Recent research has demonstrated that static magnetic fields (SMF) can generate an analgesic effect in different conditions. The present study explored effects of SMF on pain levels and expressions of P2X3 receptors in trigeminal ganglion (TG) in mice after experimental tooth movement (tooth movement induced by springs between teeth). Experiments were performed in male mice (body mass: 25-30g) and divided into SMF+force group, force group, and no force group. Exposure time was over 22h per day. Mouse Grimace Scale was used for evaluating orofacial pain levels during experimental tooth movement at 4h and 1, 3, 7, and 14 days. Meanwhile, expression levels of P2X3 receptors in the TG were evaluated by immunohistochemistry and western blotting at same time points. We finally found that during experimental tooth movement, pain levels of mice peaked at 3 days, and then decreased. While pain levels of mice were reduced in the SMF environment at 4h, 1 and 3 days, there was a significant difference at 1 and 3 days. Meanwhile, under the action of SMF, expression levels of P2X3 receptors in TG were significantly lower at 4h, 3 and 7 days. These results suggest that SMF can reduce pain levels in mice, and down-regulate P2X3 receptors in TG. Bioelectromagnetics. 38:22-30, 2017. (c) 2016 Wiley Periodicals, Inc.
Objectives: Antihypertensive therapy is effective to control blood pressure (BP) and to prevent cardiovascular events, but the further treatment strategies for patients who cannot achieve goal BP with low-dose monotherapy is still under dispute. Our study investigates the effects of high-dose amlodipine and valsartan and their low-dose combination on blood pressure variability (BPV) and pulse wave velocity (PWV) to provide references for clinical medication. Materials and Methods: This study was a prospective, randomized, parallel, case-controlled trial performed in a medical center. A total of 134 outpatients newly diagnosed with essential hypertension or receiving low-dose monotherapy were enrolled and 119 completed the trial. They were randomized into amlodipine 10 mg group (n = 40), valsartan 160 mg group (n = 38) and amlodipine 5 mg + valsartan 80 mg (n = 41) in a 1:1:1 allocation ratio for a 10-week treatment. Demographic data and laboratory indicators were collected at the randomization and 10 weeks after the treatment. The 24-hour ambulatory BP and brachial-ankle PWV were also monitored. Results: All therapies reduced systolic and diastolic BP (P < 0.05). The 24-hour systolic BPV was significantly decreased in amlodipine and combination groups (3.55 +/- 2.57, 4.11 +/- 2.20 versus 2.23 +/- 2.54 mm Hg, P < 0.05). The effects on diastolic BPV differed between different treatments. PWV was lowered by 3 antihypertensive schemes; the degree of which from strongest to weakest were valsartan, combination and amlodipine (228.87 +/- 60.41 versus 152.49 +/- 49.25 versus 99.35 +/- 35.57 cm/second, P < 0.01). Conclusions: All further strategies can effectively control BP. The combination treatment reduces both BPV and PWV noticeably, whereas double-dose amlodipine achieves the greatest BPV decrease and valsartan is best in controlling PWV.
Several imaging modalities have been widely applied for the detection of cancer and its pathological activity in combination with probes capable of improving the contrast between healthy and cancerous tissues. Biocompatible polymeric nanoassemblies have been developed for precise detection of malignant tumors by enhancing the selectivity and sensitivity of the imaging. Exploiting the compartmentalized structure of the nanoassemblies advantageously allows delivering both imaging and therapeutic agents for cancer multifunctional imaging and theranostics, i.e., the combination of therapy and diagnosis tool on a single platform. Thus, nanoassemblies have high potential not only for cancer molecular imaging but also for tracing nanoparticles in biological systems, studying their biological pathways, gathering pathological information, monitoring therapeutic effects, and guiding pinpoint therapies. In this review, polymeric nanoassemblies for optical imaging, magnetic resonance imaging, multifunctional imaging, and image-guided therapy, emphasizing their role in cancer diagnosis and theranostics are highlighted.
Aim: Inflammation plays a role in secondary brain injury after intracerebral hemorrhage (ICH). We aimed to determine the prognostic significance of admission white blood cell (AWC), neutrophil count (ANC), lymphocyte count, monocyte count and neutrophil to lymphocyte ratio (NLR) for 90-day outcome after ICH. Patients & methods: A total of 336 patients with spontaneous ICH were retrospectively investigated. Clinical outcome was assessed by modified Rankin Scale at 90 days. Results: Multivariate analysis showed that higher AWC, ANC, NLR were independently associated with mortality and worse outcome. Moreover, NLR showed a higher predictive ability in mortality than in poor outcome in receiver operating characteristic analysis. Linear regression analyses revealed admission Glasgow Coma Scale score and ICH volume were mostly correlated with these indices. Conclusion: Elevated levels of AWC, ANC and NLR were independently related to poor 90-day outcome after ICH. NLR may be a novel inflammatory biomarker following ICH.
At present, there is no specific anti-metastasis drug in HCC treatment. Drugs used for primary HCC tumors and tumor metastasis are very similar, among which cytotoxic drugs are prevalent, such as cisplatin, doxorubicin and 5-FU. The EGFR pathway plays an important role in promoting hepatocellular carcinoma (HCC) metastasis. Hence, development of non-toxic anti-metastasis drugs, such as EGFR or downstream pathways inhibitors, is of great importance. In our present study, we found non-toxic dose of liposomal honokiol (LH) could inhibit the HCC metastasis by destabilizing EGFR and inhibiting the downstream pathways. Non-toxic dose of LH significantly inhibited the motility, migration and lamellipodia formation of HepG2 cells in vitro and decreased extravasation of HepG2 cells in a novel metastasis model of transgenic zebrafish. In two lung metastasis models (HepG2 and B16F10) and a spontaneous metastasis model of HepG2 cells, LH remarkably inhibited pulmonary metastasis and regional lymph nodes metastasis without obvious toxicity. Further study showed that destabilizing EGFR and inhibiting the downstream pathways were the main mechanisms of non-toxic dose of LH on metastasis inhibition. Our results provide the preclinical rationale and the underlying mechanisms of LH to suppress HCC metastasis, implicating LH as a potential therapeutic agent to block HCC metastasis without severe side effects.
alpha-Calcitonin gene-related peptide (alpha-CGRP) plays a significant pathophysiological role in bone development, metabolism and remodeling around dental implants. However, the half-life of alpha-CGRP in plasma is only 10 min, which affects its long-time application and an alternative approach should be developed to deliver alpha-CGRP over long periods of time. The aim of this study is to investigate whether a lentiviral alpha-CGRP overexpression vector system can express this target-gene longer at peri-implant sites, thus enhancing osseointegration. Animals were divided to the following groups: alpha-CGRP(-/-), alpha-CGRP(-/-) with lentivirus transfection and alpha-CGRP(+/+) mice. MS Spectrum imaging observations identified the successful transfection of alpha-CGRP around experimental implants inserted in the femurs at 5 days after injection. Histomorphometrical analysis indicated an increase of bone-implant contact (BIC) at 1-month healing in the transfection group. Moreover, real-time RT-PCR and western blot results of bone-related markers Runx2, Osterix, and BSP levels elevated in lentivirus-transfected mice at 21 days, compared to the untreated alpha-CGRP(-/-) mice. There was no significant difference between the transfection group and alpha-CGRP(+/+) group. Further alpha-CGRP protein detection confirmed the persistent expression of this transgene at 21 days post-operatively. These results suggest that this lentiviral vector system expresses alpha-CGRP in an effective, appropriate and sustained manner, which might have a potential application in enhancing titanium implant osseointegration. (C) 2016 Elsevier Inc. All rights reserved.
Intraoperative frozen pathology is critical when a breast tumor is not diagnosed before surgery. However, frozen tumor tissues always present various microscopic morphologies, leading to a high misdiagnose rate from frozen section examination. Thus, we aimed to identify breast tumors using bioimpedance spectroscopy (BIS), a technology that measures the tissues' impedance. We collected and measured 976 specimens from breast patients during surgery, including 581 breast cancers, 190 benign tumors, and 205 normal mammary gland tissues. After measurement, Cole-Cole curves were generated by a bioimpedance analyzer and parameters R-0/R-infinity, f(c), and alpha were calculated from the curve. The Cole-Cole curves showed a trend to differentiate mammary gland, benign tumors, and cancer. However, there were some curves overlapped with other groups, showing that it is not an ideal model. Subsequent univariate analysis of R-0/R-infinity, f(c), and alpha showed significant differences between benign tumor and cancer. However, receiver operating characteristic (ROC) analysis indicated the diagnostic value of f(c) and R-0/R-infinity were not superior to frozen sections (area under curve [AUC]= 0.836 and 0.849, respectively), and a was useless in diagnosis (AUC= 0.596). After further research, we found a scatter diagram that showed a synergistic effect of the R-0/R-infinity, and f(c), in discriminating cancer from benign tumors. Thus, we used multivariate analysis, which revealed that these two parameters were independent predictors, to combine them. A simplified equation, RF' = 0: 2f (c) + 3: 6R(0)/R-infinity, based on multivariate analysis was developed. The ROC curve for RF' showed an AUC= 0.939, and the sensitivity and specificity were 82.62% and 95.79%, respectively. To match a clinical setting, the diagnostic criteria were set at 6.91 and 12.9 for negative and positive diagnosis, respectively. In conclusion, RF' derived from BIS can discriminate benign tumor and cancers, and integrated criteria were developed for diagnosis.
Objective Postablation whole-body scintigraphy, which is performed 5-7 days after administration of ablation activity of radioactive iodine-131 (I-131) in patients with thyroid cancer, is considered a routine procedure for remnant ablation and a useful tool for disease staging. However, the relationship of preablation stimulated thyroglobulin (s-Tg) levels with postablation scintigraphic findings has not been evaluated. The current study was designed to determine the diagnostic value of postablation I-131 scintigraphy during initial staging and risk stratification in intermediate-risk papillary thyroid cancer (PTC) patients with pre-ablation s-Tg < 1 ng/ml at the time of ablation. Design From January 2013 to July 2015, consecutive PTC patients at intermediate-risk of recurrence according to American Thyroid Association criteria were prospectively recruited. Patients had to have pre-ablation s-Tg < 1 ng/ml in the absence of anti-Tg antibody at the time of ablation. Systematic pre-ablation neck ultrasonography was performed for each patient. Postablation whole-body planar scintigraphy was obtained 5 days after administration of ablation activity of I-131. Single photon emission computed tomography/low-dose computed tomography was added for patients whose planar findings were inconclusive. Results Among 756 patients ablated, 240 (31.7%) patients were eligible for the analysis. Pre-ablation neck ultrasonography revealed lymph node metastases in eight of the 240 patients. Postablation scintigraphy showed ectopic neck uptake corresponding to the lymph nodes seen by ultrasonography in four patients and revealed neck lymph node metastases in another two patients whose ultrasonography findings were negative. None of the 240 patients showed distant metastasis on postablation scintigraphy. Neither staging nor initial risk stratification was altered by postablation scintigraphy in the included patients with pre-ablation s-Tg < 1 ng/ml. Conclusions As postablation whole-body scintigraphy played a minimal role in improving staging or initial risk stratification in intermediate-risk PTC patients with pre-ablation s-Tg < 1 ng/ml, we propose that postablation scintigraphy may be omitted in this group of patients. Multi-institutional larger studies are necessary to draw definitive conclusions.
Deferoxamine (DFO), an iron chelator, is commonly used to remove excess iron from the body. DFO has also been demonstrated to have anti-tumor effect. However, there is no available report on the effect of deferoxamine on mesenchymal stromal cells (MSCs). In this study, we first isolated tumor-associated MSCs (TAMSCs) from EG-7 tumors, which were positive for CD29, CD44, CD73, CD90 and CD105. Ex vivo cultured stem cells derived from tumor and bone marrow compartment were exposed to DFO. We demonstrated that DFO had growth-arresting and apoptosis-inducing effect on TAMSCs and bone marrow MSCs (BMMSCs). DFO also influenced the expression pattern of adhesion molecule VCAM-1 on both TAMSCs and BMMSCs. Notwithstanding its widespread use, our results here warrants caution in the application of DFO, and also highlights the need for careful evaluation of the bone marrow compartment in patients receiving DFO treatment. (C) 2016 Elsevier B.V. All rights reserved.